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Stewardship / Resistance Scan for Jun 25, 2021

New C difficile guidelines favor fidaxomicin over vancomycin

Guidelines published yesterday by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) contain three new recommendations for treating adults who have Clostridioides difficile infection (CDI).

For both initial and recurring CDI cases, the new guidelines, published in Clinical Infectious Diseases, now recommend using the antibiotic fidaxomicin rather than vancomycin, though in both cases vancomycin is considered an acceptable alternative.

The previous CDI guidelines, issued in 2018, recommended either drug for initial and recurrent CDI, but the authors of the new guidelines—a panel of US, UK, and Canadian experts—say a review of additional evidence from randomized controlled trials indicates fidaxomicin is now the preferred option, though the recommendation is conditional, with moderate and low certainty evidence. The panel also notes that the cost of fidaxomicin, which was approved by the Food and Drug Administration (FDA) in 2011, may be prohibitive without adequate insurance coverage.

The third new recommendation is that in patients who’ve had a recurrent CDI episode within the past 6 months or have other risk factors for recurrence, clinicians should use the monoclonal antibody bezlotoxumab in conjunction with standard-of-care (SOC) antibiotics, rather than SOC antibiotics alone. This recommendation is also conditional, with a very low certainty of evidence, and the panel notes that the FDA warns against using bezlotoxumab in patients with congestive heart failure unless the benefit outweighs the risk.

The previous recommendation of fecal microbiota transplantation (FMT) in patients who have had several bouts of CDI and have failed appropriate antibiotic treatment remains unchanged, although the authors point out that the FDA has issued three warnings on FMT since 2018. The warnings concern the potential for transmission of pathogenic bacteria and SARS-CoV-2.

CDI is the leading cause of diarrhea in hospitals and one of the most common healthcare-associated infections. The Centers for Disease Control and Prevention estimates that 461,000 cases occur annually in the United States.
Jun 24 Clin Infect Dis abstract

Trial: 7 days of doxycycline preferable to azithromycin for rectal chlamydia

The results of a randomized clinical trial conducted in Australia indicate a 7-day course of doxycycline is superior to single-dose azithromycin for treating rectal chlamydia in men who have sex with men, researchers reported yesterday in the New England Journal of Medicine.

The double-blind, randomized trial was conducted at five sexual health clinics in Australia from August 2016 through August 2019 to determine which of the two regimens, which are both recommended for treatment of rectal chlamydia, is more efficacious.

While single-dose azithromycin has been an attractive therapy because of its simplicity, recent observational data has indicated that 7 days of doxycycline may be up to 20% more effective. But no randomized trials to date have been conducted. Enrollment in the trial was limited to asymptomatic chlamydia because more than 85% of rectal chlamydia infections among men who have sex with men are asymptomatic.

A total of 625 men were enrolled in the trial, and primary outcome data were available for 290 in the doxycycline group and 297 in the azithromycin group. In the modified intention-to-treat population, microbiologic cure occurred in 96.9% of men in the doxycycline group and 76.4% of men in the azithromycin group, for an adjusted risk difference of 19.9 percentage points. In the per-protocol population, microbiologic cure was observed in 95.7% of men in the doxycycline group and 73.3% in the azithromycin group, for an adjusted risk difference of 21.3 percentage points. Adverse events, including nausea, diarrhea, and vomiting, were reported in 33.8% of men in the doxycycline group and 45.1% in the azithromycin group.

The study authors say azithromycin will still have a place for the treatment of chlamydia during pregnancy, when doxycycline is not recommended, and in patients who are allergic to doxycycline.
Jun 24 N Engl J Med abstract

Resistant bacteria in veterinary workers linked to contact with animals

Nearly 1 in 10 veterinary workers in the Netherlands carries a multidrug-resistant strain of intestinal bacteria, almost twice the prevalence of the general population, Dutch researchers reported in a study being presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

To get a better understanding of the extent of transmission of intestinal bacteria carrying extended-spectrum beta-lactamase (ESBL) and AmpC genes between humans and animals, researchers from the National Institute for Public Health and the Environment collected stool samples from 482 veterinary workers and conducted whole-genome sequencing to identify the species of bacteria and detect the presence of ESBL/AmpC. They also analyzed questionnaires filled out by veterinary staff on their contact with animals at work and home, health status, and travel history to identify other risk factors.

The analysis found that 47 of 482 (9.8%) veterinary workers were colonized with at least one ESBL/AmpC-producing Enterobacterales. The most common ESBL genes detected were blaCTX-M-15 (26 samples), blaCTX-M-14 (7 samples), and blaDHA-1 (4 samples). The most common Escherichia coli strain identified was ST131, a frequent cause of human urinary tract infections. In addition, 16 of 33 (48.5%) who tested positive did so again 6 months later, and in 14 of those vet workers the same ESBL gene and E coli strain was identified. The analysis also found that 17% of household members of the participants carried ESBL-producing bacteria.

Among the risk factors identified was travel to Asia, Africa, and Latin America, along with reported stomach/bowel problems in the previous 4 weeks, but the study authors say those risk don’t fully account for the presence of ESBL/AmpC-producing bacteria.

“So it seems highly likely that occupational contact with animals in the animal healthcare setting can provide a reservoir for ESBL-producing bacteria, despite the absence of specific occupational risk factors, such as contact with specific animal species,” lead study author Anouk Meijs, MSc, said in an ECCMID press release.

The authors note that the observational study does not prove that close contact with animals was responsible for colonization with ESBL-producing bacteria.

ECCMID is being held online this year from Jul 9 through Jul 12.
Jun 23 ECCMID press release

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